Category: 212268-13-8

Hameed P, Shahul; Patil, Vikas; Solapure, Suresh; Sharma, Umender; Madhavapeddi, Prashanti; Raichurkar, Anandkumar; Chinnapattu, Murugan; Manjrekar, Praveena; Shanbhag, Gajanan; Puttur, Jayashree; Shinde, Vikas; Menasinakai, Sreenivasaiah; Rudrapatana, Suresh; Achar, Vijayashree; Awasthy, Disha; Nandishaiah, Radha; Humnabadkar, Vaishali; Ghosh, Anirban; Narayan, Chandan; Ramya, V. K.; Kaur, Parvinder; Sharma, Sreevalli; Werngren, Jim; Hoffner, Sven; Panduga, Vijender; Kumar, C. N. Naveen; Reddy, Jitendar; Kumar KN, Mahesh; Ganguly, Samit; Bharath, Sowmya; Bheemarao, Ugarkar; Mukherjee, Kakoli; Arora, Uma; Gaonkar, Sheshagiri; Coulson, Michelle; Waterson, David; Sambandamurthy, Vasan K.; de Sousa, Sunita M. published the artcile< Novel N-Linked Aminopiperidine-Based Gyrase Inhibitors with Improved hERG and in Vivo Efficacy against Mycobacterium tuberculosis>, Safety of 5-Fluoropyridine-2,3-diamine, the main research area is aminopiperidinyl quinolone naphthyridone Mycobacterium tuberculosis bactericide DNA gyrase inhibitor.

DNA gyrase is a clin. validated target for developing drugs against Mycobacterium tuberculosis (Mtb). Despite the promise of fluoroquinolones (FQs) as anti-tuberculosis drugs, the prevalence of pre-existing resistance to FQs is likely to restrict their clin. value. We describe a novel class of N-linked aminopiperidinyl alkyl quinolones and naphthyridones that kills Mtb by inhibiting the DNA gyrase activity. The mechanism of inhibition of DNA gyrase was distinct from the fluoroquinolones, as shown by their ability to inhibit the growth of fluoroquinolone-resistant Mtb. Biochem. studies demonstrated this class to exert its action via single-strand cleavage rather than double-strand cleavage, as seen with fluoroquinolones. The compounds are highly bactericidal against extracellular as well as intracellular Mtb. Lead optimization resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability. Compounds from this series are efficacious in various murine models of tuberculosis (e.g., compound I).

Journal of Medicinal Chemistry published new progress about Antibacterial agents. 212268-13-8 belongs to class pyridine-derivatives, and the molecular formula is C5H6FN3, Safety of 5-Fluoropyridine-2,3-diamine.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Georgiou, Charis; McNae, Iain; Wear, Martin; Ioannidis, Harris; Michel, Julien; Walkinshaw, Malcolm published the artcile< Pushing the Limits of Detection of Weak Binding Using Fragment-Based Drug Discovery: Identification of New Cyclophilin Binders>, Category: pyridine-derivatives, the main research area is drug design diaminopyridine cyclophilin binding; PPIases; cyclophilin inhibitors; fragment-based drug discovery; free energy calculations; protein–ligand X-ray crystallography.

Fragment-based drug discovery is an increasingly popular method to identify novel small-mol. drug candidates. One of the limitations of the approach is the difficulty of accurately characterizing weak binding events. This work reports a combination of X-ray diffraction, surface plasmon resonance experiments and mol. dynamics simulations for the characterization of binders to different isoforms of the cyclophilin (Cyp) protein family. Although several Cyp inhibitors have been reported in the literature, it has proven challenging to achieve high binding selectivity for different isoforms of this protein family. The present studies have led to the identification of several structurally novel fragments that bind to diverse Cyp isoforms in distinct pockets with low millimolar dissociation constants A detailed comparison of the merits and drawbacks of the exptl. and computational techniques is presented, and emerging strategies for designing ligands with enhanced isoform specificity are described.

Journal of Molecular Biology published new progress about Cyclophilins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (inhibitors). 212268-13-8 belongs to class pyridine-derivatives, and the molecular formula is C5H6FN3, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Tatipaka, Hari Babu; Gillespie, J. Robert; Chatterjee, Arnab K.; Norcross, Neil R.; Hulverson, Matthew A.; Ranade, Ranae M.; Nagendar, Pendem; Creason, Sharon A.; McQueen, Joshua; Duster, Nicole A.; Nagle, Advait; Supek, Frantisek; Molteni, Valentina; Wenzler, Tanja; Brun, Reto; Glynne, Richard; Buckner, Frederick S.; Gelb, Michael H. published the artcile< Substituted 2-Phenylimidazopyridines: A New Class of Drug Leads for Human African Trypanosomiasis>, COA of Formula: C5H6FN3, the main research area is phenylimidazopyridine derivative preparation SAR human trypanosomiasis.

A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of human African trypanosomiasis, led to the identification of substituted 2-(3-aminophenyl)-oxazolopyridines as a starting point for hit-to-lead medicinal chem. A total of 110 analogs were prepared, which led to the identification of I, a substituted 2-(3-aminophenyl)-imidazopyridine. This compound showed antiparasitic activity in vitro with an EC50 of 2 nM and displayed reasonable druglike properties when tested in a number of in vitro assays. I was orally bioavailable and displayed good plasma and brain exposure in mice. I cured mice infected with Trypanosoma brucei when dosed orally down to 2.5 mg/kg. Given its potent antiparasitic properties and its ease of synthesis, I represents a new lead for the development of drugs to treat human African trypanosomiasis.

Journal of Medicinal Chemistry published new progress about Drug bioavailability. 212268-13-8 belongs to class pyridine-derivatives, and the molecular formula is C5H6FN3, COA of Formula: C5H6FN3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Hameed P, Shahul; Raichurkar, Anandkumar; Madhavapeddi, Prashanti; Menasinakai, Sreenivasaiah; Sharma, Sreevalli; Kaur, Parvinder; Nandishaiah, Radha; Panduga, Vijender; Reddy, Jitendar; Sambandamurthy, Vasan K.; Sriram, D. published the artcile< Benzimidazoles: Novel Mycobacterial Gyrase Inhibitors from Scaffold Morphing>, Formula: C5H6FN3, the main research area is benzimidazole DNA gyrase inhibitor scaffold morphing Mycobacterium; DNA gyrase; NBTIs; Tuberculosis; aminopiperidines; benzimidazoles; type II topoisomerases.

Type II topoisomerases are well conserved across the bacterial species, and inhibition of DNA gyrase by fluoroquinolones has provided an attractive option for treatment of tuberculosis (TB). However, the emergence of fluoroquinolone-resistant strains of Mycobacterium tuberculosis (Mtb) poses a threat for its sustainability. A scaffold hopping approach using the binding mode of novel bacterial topoisomerase inhibitors (NBTIs) led to the identification of a novel class of benzimidazoles as DNA gyrase inhibitors with potent anti-TB activity. Docking of benzimidazoles to a NBTI bound crystal structure suggested that this class of compound makes key contacts in the enzyme active site similar to the reported NBTIs. This observation was further confirmed through the measurement of DNA gyrase inhibition, and activity against Mtb strains harboring mutations that confer resistance to aminopiperidines based NBTIs and Mtb strains resistant to moxifloxacin. Structure-activity relationship modification at the C-7 position of the left-hand side ring provided further avenue to improve hERG selectivity for this chem. series that has been the major challenges for NBTIs.

ACS Medicinal Chemistry Letters published new progress about DNA gyrases Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (inhibitors). 212268-13-8 belongs to class pyridine-derivatives, and the molecular formula is C5H6FN3, Formula: C5H6FN3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Kumar, Manoj; Pandey, Sushil K.; Chaudhary, Neha; Mishra, Anand; Gupta, Deepshikha published the artcile< Highly efficient method for the synthesis of substituted benzimidazoles using sodium metabisulfite adsorbed on silica gel>, Application In Synthesis of 212268-13-8, the main research area is benzimidazole preparation green chem; benzaldehyde heterocyclization phenylenediamine sodium metabisulfite silica.

A simple efficient and economical method is established to synthesize N-(un)substituted benzimidazoles from the corresponding benzaldehydes and N-(un)substituted o-phenylenediamines in moderate to excellent yields using sodium metabisulfite adsorbed on silica gel in ethanol. Most of the reactions are completed at ambient temperature with easy product isolation.

Results in Chemistry published new progress about Aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 212268-13-8 belongs to class pyridine-derivatives, and the molecular formula is C5H6FN3, Application In Synthesis of 212268-13-8.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Nunez Alonso, David; Perez-Torralba, Marta; Claramunt, Rosa M.; Torralba, M. Carmen; Delgado-Martinez, Patricia; Alkorta, Ibon; Elguero, Jose; Roussel, Christian published the artcile< Regiospecific Synthesis and Structural Studies of 3,5-Dihydro-4H-pyrido[2,3-b][1,4]diazepin-4-ones and Comparison with 1,3-Dihydro-2H-benzo[b][1,4]diazepin-2-ones>, Application of C5H6FN3, the main research area is regioselective preparation pyridodiazepinone; diaminopyridine Et aroylacetate cyclocondensation mol modeling.

Nine 3,5-dihydro-4H-pyrido[2,3-b][1,4]diazepin-4-ones, some of which contain fluoro-substituents, have been regiospecifically prepared by reaction of 2,3-diaminopyridines with Et aroylacetates. In two cases, open intermediates have been isolated and these are related to the reaction pathway. The X-ray crystal structure of 1-methyl-4-phenyl-3,5-dihydro-4H-pyrido[2,3-b][1,4]diazepin-4-one has been solved (formula, C15H13N3O; crystal system, monoclinic; space group, C2/c). This is an asym. unit constituted by a single nonplanar mol. and its conformational enantiomer due to the presence of the seven-membered diazepin-2-one moiety, which introduces a certain degree of torsion in the adjacent pyridine ring. The 1H, 13C, 15N, and 19F NMR spectra were obtained and the chem. shifts, together with those of the previously published 1,3-dihydro-2H-benzo[b][1,4]diazepin-2-ones, i.e., a total of 544 values, were successfully compared with the chem. shifts calculated at the gauge invariant AO (GIAO)/Becke, three-parameter, Lee-Yang-Parr (B3LYP)/6-311++G(d,p) level. The seven-membered ring inversion barrier in 5-benzyl-2-phenyl-3,5-dihydro-4H-pyrido[2,3-b][1,4]diazepin-4-one was determined and, in conjunction with the data from the literature, compared with the B3LYP/6-311++G(d,p) computed values. This allowed the determination of several structural effects. The rotation about the exocyclic N1-CR bond was also calculated and its dynamic properties were discussed.

ACS Omega published new progress about Crystal structure. 212268-13-8 belongs to class pyridine-derivatives, and the molecular formula is C5H6FN3, Application of C5H6FN3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Mowat, Jeffrey; Ehrmann, Alexander H. M.; Christian, Sven; Sperl, Carolyn; Menz, Stephan; Guenther, Judith; Hillig, Roman C.; Bauser, Marcus; Schwede, Wolfgang published the artcile< Identification of the Highly Active, Species Cross-Reactive Complex I Inhibitor BAY-179>, Recommanded Product: 5-Fluoropyridine-2,3-diamine, the main research area is BAY179 complex I inhibitor anticancer amide isostere.

Mitochondria are key regulators of energy supply and cell death. Generation of ATP within mitochondria occurs through oxidative phosphorylation (OXPHOS), a process which utilizes the four complexes (complex I-IV) of the electron transport chain and ATP synthase. Certain oncogenic mutations (e.g., LKB1 or mIDH) can further enhance the reliance of cancer cells on OXPHOS for their energetic requirements, rendering cells sensitive to complex I inhibition and highlighting the potential value of complex I as a therapeutic target. Herein, we describe the discovery of a potent, selective, and species cross-reactive complex I inhibitor. A high-throughput screen of the Bayer compound library followed by hit triaging and initial hit-to-lead activities led to a lead structure which was further optimized in a comprehensive lead optimization campaign. Focusing on balancing potency and metabolic stability, this program resulted in the identification of BAY-179, an excellent in vivo suitable tool with which to probe the biol. relevance of complex I inhibition in cancer indications.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 212268-13-8 belongs to class pyridine-derivatives, and the molecular formula is C5H6FN3, Recommanded Product: 5-Fluoropyridine-2,3-diamine.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Xie, Dongsheng; Lu, Jun; Xie, Jin; Cui, Junjun; Li, Teng-Fei; Wang, Yan-Chao; Chen, Yuan; Gong, Nian; Li, Xin-Yan; Fu, Lei; Wang, Yong-Xiang published the artcile< Discovery and analgesic evaluation of 8-chloro-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione as a novel potent D-amino acid oxidase inhibitor>, Recommanded Product: 5-Fluoropyridine-2,3-diamine, the main research area is chlorodihydro pyridopyrazine dione preparation amino acid oxidase inhibitor; 5-Azaquinoxaline-2,3-diones; 8-Chloro-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione; Analgesic effects; D-amino acid oxidase; DAAO inhibitors.

A series of 5-azaquinoxaline-2,3-dione derivatives were synthesized and evaluated on D-amino acid oxidase (DAAO) inhibition as potential α-hydroxylactam-based inhibitors. The potent inhibitory activities in vitro suggested that 5-nitrogen could significantly enhance the binding affinity by strengthening relevant hydrogen bond interactions. The analgesic effects of intrathecal and systemic injection of 8-chloro-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione, a representative mol. of 5-azaquinoxaline-2,3-dione, were investigated in rodents. This research not only confirmed the analgesic effect of the DAAO inhibitors but provided a new class of chem. entities with oral application potential for the treatment of chronic pain and morphine analgesic tolerance.

European Journal of Medicinal Chemistry published new progress about Analgesics. 212268-13-8 belongs to class pyridine-derivatives, and the molecular formula is C5H6FN3, Recommanded Product: 5-Fluoropyridine-2,3-diamine.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem